Malaria is responsible for approximately 2 million deaths per year worldwide, mostly African children under 5 years old, and places an enormous public health burden on many of the world's poorest countries. This burden is increasing at an alarming rate, as drug resistance in both the parasite and its mosquito vectors spreads, exacerbating the urgent need for an effective vaccine.
The most promising blood stage vaccine candidates examined so far are merozoite surface protein 1 (MSP1) and an apical membrane antigen (AMA1). Humoral immune responses targeting these surface antigens are found to be correlated with reduced disease incidence, and in vitro, such antibodies can inhibit parasite re-invasion of red blood cells (RBC) [1-3]. However, these antigen genes generally display a disproportionately high number of non-synonymous single nucleotide polymorphisms (nsSNPs) compared to genes coding for proteins that are not accessible to immune effectors [4-6], and some of these nsSNPs encode radical amino acid substitutions that clustered within the regions of the protein most accessible to the host immune system [7]. Such amino acid polymorphisms could function in immune evasion by altering both B and T cell epitopes [4,8]. It is now generally accepted that any functional malaria vaccine will need to be composed of several allelic types of each target antigen in the hope of inducing a multi-allelic response and/or conserved regions of several target antigens.
More particularly, there exists a need in the art for antigens that can be used in the diagnosis and treatment of malaria and in particular of Plasmodium falciparum malaria and Plasmodium vivax malaria. In particular, there is a need for conserved antigens associated with specific immune responses that confer protection from disease in endemic regions, and the assessment of their suitability as components of a multi-valiant malaria vaccine.